A unique class of highly oxygenated diterpenoids represented by grayanotoxin and vinigrol has been exhibited remarkable physiological activity. Their remarkable physiological activity and complicated structure pose these molecules as very challenging targets for total synthesis. We have demonstrated the powerful influence of appropriately positioned hydroxyl groups in controlling the stereochemical outcome of the SmI2-mediated reductive couplings. In all cases of these hydroxyl-directed transformations, excellent diastereoselectivity was achieved. The impact which this new methodology on synthetic organic chemistry has is clearly evident from its applicability to total synthesis, one notable example being grayanotoxin. Furthermore, it was found that the introduction of a conformational constrain greatly enhances the ability of acyclic precursors to undergo SmI2-promoted reductive cyclization of medium rings. The 8-6 fused ring system of vinigrol was synthesized through the efficient cyclization of the 8-membered ring using an SmI_2-induced coupling.